This is a proposal to renew a K-12 grant that provides support for career development in translational research for five senior fellows or junior faculty members in the multidisciplinary clinical research programs (including surgery, radiation oncology, and medical and pediatric oncology) of the Dana Farber/Harvard Cancer Center (DF/HCC). The DF/HCC is a consortium of Harvard Medical School (HMS), the Harvard School of Public Health (HSPH), and the primary HMS teaching hospitals, including the Dana-Farber Cancer Institute (DFCI), Brigham and Women's Hospital (BWH), Massachusetts General Hospital (MGH), Beth Israel-Deaconess Hospital (BID), and The Children's Hospital (CH). This proposal would support physician investigators during critical years of post fellowship training and career development, with the intent of their bringing applications of cancer biology into use for treating cancer. Thus the training program focuses on preparing for independent careers in the development of new agents targeted against angiogenesis, signal transduction and activated growth factor pathways, DNA repair defects, and other features of tumor biology. Depending on prior laboratory experience, candidates will pursue laboratory training related to their clinical interests, as in molecular oncology and genetics, pharmacokinetics, or clinical immunology, as well as didactic coursework in biostatistics and clinical trial design, as part of their development plan. Each participant will design and manage clinical trials that express the particular focus of his/her biological interest. Our K12 Advisory Committee will carefully monitor candidate's progress including research productivity didactic preparation, and mentorship by biostatistical, clinical and laboratory investigators. The advisory committee will be composed of faculty from the major clinical disciplines (medical and pediatric oncology, surgery, and radiation oncology), basic science, translational research, biostatistics, and clinical trials management. Progress of awardees will be monitored through regular written reports from trainees and mentors, research seminars presented by trainees, and a review of published work. We will aggressively recruit applications from women and minority candidates through our Cancer Center's Initiative to Eliminate Disparities in Cancer. Relevance to public health: This project helps to train young physicians for a future career in clinical research and to enhance their knowledge and expertise in the treatment of cancer.